The proposed MFB center will be to coordinate and initiate comparative toxicological and pharmacological research on an organ system level. Many toxicants reach man through the aquatic food chain and with the growing importance of fcod from the sea, this food chain can provide a sensitive indicator of organ toxicity to man as well as an indicator of accumulation of toxicant. With the very large variety of species, aquatic organisms can be selected for models to study the effect of toxicants on man. Specifically, comparative studies will be conducted on organ function and operation, including influence of organ operation by physical and chemical factors in the environment. Research concerning organ function, the normal action of the organ, is necessary for comparisons between aquatic animals and man. Organ operation, the processes involved within the organ's function, may then be assessed with regard to the impact of environmental changes. These changes will be studied with regard to understanding how they may be extrapolated for man. It is recognized that the center would be the core unit which would function to coordinate and focus the research to assure meaningful comparative studies of understanding how the toxicant might affect man. The action of environmental factors on organ operation will be investigated at several levels, such as effects on transport of material in and out of the organ, metabolic changes and alterations as influenced by hypoplasia, hyperplasia or neoplasia. Alterations of mechanisms of action resulting from environmental exposure in aquatic animals will be studied and compared with analogous changes in mammals, particularly man.